Summary

Every cell of your body was generated by cell division, forming a lineage tree that goes back to the fertilized egg. Mutations are introduced by errors in DNA replication at every cell division, as well as by mutational processes that operate continuously, such as exposure to ultraviolet light. As a consequence, every cell may have its own unique genome, with potentially distinct gains and losses of function. Furthermore, these mutations create a record of the developmental ancestry of each cell, which can be used to reconstruct their lineage tree. Now, on page 94 of this issue, Lodato et al. use single-cell whole-genome sequencing to show these processes at work in the human brain (1). This is important because many unresolved questions in human biology and medicine are in fact questions about the human cell lineage tree in development and disease (2). Charles Darwin famously drew the first phylogenetic tree in 1837. This was only a month after he had started his first notebook on evolution, but the idea had already gelled in his mind that all species are linked like the branches on a tree. A few years later, around the time he was completing On the Origin of Species, a similarly remarkable insight was forming among a small group of scientists in Germany. Theodor Schwann and Matthias Schleiden had realized that both plants and animals are made of nothing but cells, but it was Robert Remak who showed that new cells arise through binary fission. These insights lead to the conclusion that every individual is also a tree—a cell lineage tree.